Tailoring N, N, N-trimethyl chitosan nanospheres as an efficient drug carrier to overcome endothelial barrier

Endothelial barriers, integral components of tissue barriers, are densely packed with adherens junction and tight junction proteins, hindering the passage of drugs to target sites. Herein, a novel nanosphere comprising N, N, N-trimethylated chitosan (TMC), with the size of 51 ± 8 nm and zeta potential of 13.2 ± 5.3 mV, has been engineered as a drug carrier to facilitate the transport of hydrophobic drugs, that is, curcumin, across endothelial barriers efficiently. The effects of pH value and temperature on the release kinetics of curcumin from TMC nanospheres have been studied. In addition, the transportation of TMC nanospheres across an in vitro endothelial barrier was evaluated over a 72-h period. The integrity of the in vitro endothelial barrier was assessed before and after the transport of TMC nanospheres by using transepithelial electrical resistance measurements and immunofluorescence staining of tight junction proteins. The results reveal that TMC nanospheres significantly enhance the transport of curcumin across the endothelial barrier, with approximately 30% of curcumin released as compared to less than 3.3% across the barrier without the assistance of TMC nanospheres. This investigation underscores the potential of small-sized TMC nanospheres to enhance the transport of hydrophobic drugs across endothelial barriers.